Berkley Gryder, PhD, a member of the Case CCC Cancer Genomics and Epigenomics Program and assistant professor in the Department of Genomics at Case Western Reserve University School of Medicine, received a prestigious five-year, $1 million All-Star grant from the V Foundation for Cancer Research.
The award will support the advancement of a targeted therapeutic strategy for fusion-positive rhabdomyosarcoma (FP-RMS), an aggressive pediatric sarcoma driven by the PAX3-FOXO1 fusion oncoprotein. The All-Star grant represents a reinvestment in a previous V Scholar or translational grant recipient who is invited to apply for additional support.
Although PAX3-FOXO1 has long been considered an undruggable transcription factor, Gryder’s project builds on his team’s discovery that FP-RMS exhibits a selective dependence on CBP/p300-mediated enhancer activity, a vulnerability known as enhancer addiction.
The team also identified the histone modification H2BNTac as a potential biomarker of CBP/p300 dependence and developed IHK-44, a novel CBP/p300 inhibitor that has demonstrated greater potency and selectivity in FP-RMS models than other compounds in its class.
The five-year study aims to define the chromatin mechanisms underlying enhancer addiction, validate H2BNTac as a predictive biomarker of therapeutic response, and optimize IHK-44 through medicinal chemistry, pharmacokinetic, safety, and preclinical efficacy studies using patient-derived tumor models.
Together, these aims are designed to deliver a first-in-class precision therapeutic strategy that pairs a CBP/p300 inhibitor with a companion biomarker, accelerating its potential translation into a treatment for children with FP-RMS.
The award is funded through the V Foundation’s Dick Vitale Pediatric Cancer Research Fund, established by legendary college basketball broadcaster Dick Vitale. His longstanding commitment to pediatric cancer research has helped generate significant support for innovative childhood cancer investigations.